The minor hemoglobin components, AIa plus b and AIc, increase in amount in normal subjects during in vivo red cell aging. Hemoglobin AIc differs from the major Hb A component in having a ketoamine attached to the N-terminal valine of the Beta chains. It has an increased oxygen affinity and may therefore affect oxygen delivery to the tissue. In diabetic subjects the formation of hemoglobin AIc is increased as compared to normals and the increase is correlated with the levels of blood sugar. This study proposes to determine if the formation of hemoglobin AIc is enzymatically catalyzed or results from a nonenzymic reaction. The nature of the donor hexose and the in vivo conditions which account for formation of the ketoamine will also be studied.